Effect of propofol on activation of NF-?B and the expression of Bcl-2 and Caspase-3 gene in cerebral cortex following transient focal cerebral ischemia-reperfusion in rats
- VernacularTitle:异丙酚对大鼠局灶性脑缺血再灌注时NF-?B活化和Bcl-2、Caspase-3基因表达的影响
- Author:
Chunsheng FENG
;
Haichun MA
;
Yun YUE
- Publication Type:Journal Article
- Keywords:
Propofol;
Brain ischemia;
Reperfusion injury;
NF-kappa B;
Genes, Bcl-2;
Lysteine endopeptidases
- From:
Chinese Journal of Anesthesiology
1994;0(05):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of propofol on the activation of NF-?B and the expression of Bcl-2 and Caspase-3 gene in cerebral cortex after transient focal cerebral ischemia-reperfusion (I/R) and the possible mechanism. Methods Ninety healthy male Wistar rats aged 3-4 months weighing 250-300g were randomly divided into 3 groups (n=30 each) : group Ⅰ sham operation; group Ⅱ I/R and group Ⅲ propofol + I/R. The animals were anesthetized with intraperitoneal chloral hydrate 300 mg?kg-1. Left common, internal and external carotid arteries (CCA, ICA, ECA) were exposed. Middle cerebral artery occlusion (MCAO) was produced by inserting a nylon thread, 0.26-0.28 mm in diameter and 4.0 cm in length into ICA and advancing it cranially until resistance was felt. After 2 h MCAO the nylon thread was withdrawn to allow reperfusion. In propofol group propofol 100 mg?kg-1 was given IP 10 min before MCAO. The animals were decapitated at 2, 3, 6, 12, 24 and 72 h of reperfusion (n=5 at each time point in each group) . Their brains were immediately removed for determination of translocation of NF-?B in the neurons (by immuno-histochemistry) and expression of NF-?B in cerebral cortex (by Western blotting). The expression of Bcl-2 mRNA and Caspase-3 mRNA in cerebral cortex was determined by in situ hybridization. Neurological deficit was scored and microscopic examination of ischemic cerebral cortex was performed at 24 h of reperfusion. Results In I/R group (Ⅱ) NF-?B was significantly translocated from cytoplasm into the nucleus of the neurons in the ischemic cerebral cortex during 2-24 h of reperfusion while in non-ischemic cortex NF-?B was confined to the cytoplasm. The expression of NF-?B, Bcl-2 mRNA and Caspase-3 mRNA was significantly higher in ischemic cortex than in non-ischemic cortex. Neurologic deficit scores were higher in I/R group than in sham-operation group. Microscopic examination showed congestion and edema of ischemic cerebral cortex and degeneration and necrosis of the neurons in I/R group. In group Ⅲ propofol pretreatment significantly inhibited the translocation of NF-?B, decreased expression of NF-?B and Caspase-3 mRNA and increased Bcl-2 mRNA expression as compared with I/R group (Ⅱ) . Neurologic dificit and histologic damage induced by I/R were significantly ameliorated by propofol pretreatment. Conclusion Propofol pretreatment can inhibit apoptosis of neurons induced by I/R by inhibiting the activation of NF-B, up-regulating Bcl-2 gene and down-regulating Caspase-3 gene.
